Regulation of Circadian Genes by the MAPK Pathway: Implications for Rapid Antidepressant Action

  • Xin-Ling Wang
  • Kai Yuan
  • Wen Zhang
  • Su-Xia LiEmail author
  • George Fu GaoEmail author
  • Lin LuEmail author


Accumulating evidence suggests that the circadian rhythm plays a critical role in mood regulation, and circadian disturbances are often found in patients with major depressive disorder (MDD). The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway is involved in mediating entrainment of the circadian system. Furthermore, the MAPK/ERK signaling pathway has been shown to be involved in the pathogenesis of MDD and the rapid onset of action of antidepressant therapies, both pharmaceutical and non-pharmaceutical. This review provides an overview of the involvement of the MAPK/ERK pathway in modulating the circadian system in the rapid action of antidepressant therapies. This pathway holds much promise for the development of novel, rapid-onset-of-action therapeutics for MDD.


Major depressive disorder MAPK pathway Circadian system Rapid antidepressant therapy 



This review was supported by the National Basic Research Development Program of China (2015CB856400 and 2015CB553503), the National Natural Science Foundation of China (81521063), and the Natural Science Foundation of Beijing Municipality, China (7162101).


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Copyright information

© Shanghai Institutes for Biological Sciences, CAS 2019

Authors and Affiliations

  1. 1.Savaid Medical SchoolUniversity of the Chinese Academy of SciencesBeijingChina
  2. 2.Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain ResearchPeking UniversityBeijingChina
  3. 3.National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence ResearchPeking UniversityBeijingChina
  4. 4.Key Laboratory of Pathogenic Microbiology and Immunology, Institute of MicrobiologyChinese Academy of SciencesBeijingChina
  5. 5.Chinese Center for Disease Control and PreventionBeijingChina
  6. 6.Institute of Mental Health, National Clinical Research Center for Mental Disorders, Key Laboratory of Mental Health and Peking University Sixth HospitalPeking UniversityBeijingChina

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